Ether muscarinic antagonists

本发明公开了式(I)1，4-二取代哌啶毒蕈碱性拮抗剂或其异构体、可药用盐、酯或溶剂化物，其中X为键、-O-、-S-、-SO-、-SO#-[2]-、-CO-、-C(OR#+[7])#-[2]-、-CH#-[2]-O-、-O-CH#-[2]-、-CH＝CH-、-CH#-[2]-、-CH(C#-[1]-C#-[6]烷基)-、-C(C#-[1]-C#-[6]烷基)#-[2]-、-CONR#+[17]-、-NR#+[17]CO-、-O-C(O)NR#+[17]-、-NR#+[17]C(O)-O-、-SO#-[2]NR#+[17]-或-NR#+[17]SO#-[2]-；R为环烷基、任选取代的苯基或任选取代的吡啶基；R#+[2]为H、烷基、任选取代的环烷基、环烯基、叔丁氧基羰基或任选取代的哌啶基；其余变量如说明书定义。式(I)化合物可用于治疗识别性疾病，如Alzheimer氏疾病。本发明还公开了药物组合物、制备方法以及式(I)化合物与乙酰胆碱酯酶抑制剂的组合物。∴ 1,4 Di-substituted piperidine muscarinic antagonists of formula (I) or an isomer, pharmaceutically acceptable salt, ester or solvate thereof, wherein X is a bond, -O-, -S-, -SO-, -SO2-, -CO-, -C(OR )2-, -CH2-O-, -O-CH2-, -CH=CH-, -CH2-, -CH(C1-C6 alkyl)-, -C(C1-C6 alkyl)2-, -CONR -, -NR CO-, -O-C(O)NR -, -NR C(O)-O-, -SO2NR - or -NR SO2-; R is cycloalkyl, optionally substituted phenyl or optionally substituted pyridyl; R is H, alkyl, optionally substituted cycloalkyl, cycloalkenyl, t-butoxycarbonyl or optionally substituted piperidinyl; and the remaining variables are as defined in the specification, are disclosed. Compounds of formula (I) are useful for treating cognitive disorders such as Alzheimer's disease. Also disclosed are pharmaceutical compositions, methods of preparation and combinations of compounds of formula (I) with ACh'ase inhibitors.